Document aR3RwJvLD5zpzKkJLeK4d91B

V ol. 54 March, 1059 No. 3 CHRONIC LEAD POISONING A R eview ok Seven Y ears' E xperience at the Children's H ospital, District of Columbia Georoe J . Cohen. .M.D., and W alter E. A iirens, .AI D. S ilver Spring. Md. TH E purpose* ol` this article is to review seven years' experience with the problem of chronic lead poisoning in infants and children in a large children's hospital, and to consider this experience in the light of previous reports. BACKGROUND Lead poisoning is still a significant cause of m ortality and m orbidity in children. Although only 19 eases were reported by Millichap and associates' in G reat B ritain in the 50 years ending in 1952, most American reports indi cate a much higher incidence.'-'8 W ith out question the most im portant cause of chronic lead intoxication in children is ingestion of lead-containing sub stances. Scattered small epidemics of acute intoxication due to inhalation of lead fumes from burning storage bat tery casings have been reported." ..Of the substances ingested by children, the most widely reported are paint from walls and woodwork and plas ter.1'5*T*8 Other sources are painted furniture and painted or lead toys. In earlier times, lead nipple shields and body powders containing lead were common sources. In most reported series, the age range of children with lead intoxica tion is from 1 to 4 years,3*5':*10 the time of life when incidence is highest for all acute toxic ingestions. How ever, since only small amounts of lead can be absorbed and retained at one time, the abnormal appetite, or pica, to cause toxicity, must persist for several months. The psychological background of the pica associated with chronic lead in toxication has been studied by several authors1*:*10 who have observed th at most of these children lived in blighted or slum areas where flaking paint and loose plaster were abundant. In addi tion, personal supervision was limited because of the necessity for working parents to be away from home, the large number of children in the fami lies, and the p a re n ts' ignorance of the dangers of lead ingestion. Although most of the children were apparently normal in intellectual and motor func tioning prior to illness, they were often emotionally unstable and harder to handle than their siblings. The mother-child relationship was fre quently abnormal as manifested by the THE JOURNAL OF PEDIATRICS m other's indifferent or punishing^ a t There are often no abnormal physi titude toward the child, her encour cal findings, especially when there is agement of the child's oral activity as no severe central nervous system dis a substitute for m aternal attention, ease. Among the most commonly ob an d /o r occasionally significant emo served objective signs are pallor, mo tional problems in the mother herself. tor weakness, coma, convulsions, papil Most authors have noted a higher ledema, hyperreflexia, and atax ia.1,3-8 incidence of symptoms from lead poi R espiratory center depression11 .and soning in the sum m er months.3' *5' : diaphragm atic paralysis1 have also Two possible reasons are: (1) the ef been reported. Lead lines on the fect of increased solar radiation on the gums, which are common in adult skin producing in the patient more plumbism, are quite unusual in chil vitam in D, which presum ably aids in d ren.12 l ' the absorption of lead, and (2) more The pathologic changes due to lead frequent dehydration and acidosis intoxication are in general rather which mobilize lead from depots. nonspecific.3,5' 13' 14 The b rain may There seems to be little correlation show edema, punctate hemorrhages, between the incidence of lead poison gliosis, and focal necrosis, while the ing and sex or race of the patient. liver and kidney may show character A survey of geographical distribu istic acid-fast intranuclear inclusions tion of plumbism in children is cur as well as renal tu b u la r cell abnormal rently being made by Dr. Howard M. ities. A frequent finding is degenera Cann of the Clearing House for Poison tion of an terio r horn cells. W hen tis Control Centers of the U. S. Public sues have been analyzed for lead con Health Service. ten t,3' 7 the bones have contained the Symptoms, when present, almost highest concentration, the liver and always relate to the gastrointestinal kidneys next; the brain, even in the or central nervous systems.1'6' 8Among presence of severe clinical encephalop the frequent and significant symptoms athy, contained the least amount. are anorexia, vomiting, constipation, In one of our cases of fatal lead abdominal pain, irritability, convul encephalitis previously reported by sions, drowsiness, incoordination, and Rice and associates,13 no lead was ex pallor. Less commonly reported symp tracted from the brain although high toms include personality change, trem levels were found in bone, liver, and ors, and diarrhea. A prodrome of kidneys. These findings suggest either minor gastrointestinal symptoms, such that lead is not a direct toxic agent as constipation or abdominal pain, and to brain tissue, or th at the brain is central nervous symptoms, such as so sensitive th at even m inute amounts lethargy, may precede by as much as can cause significant damage. two weeks the onset of more serious Almost all children with chronic symptoms of vomiting, coma, or con plumbism have a significant anemia- vulsions. Although the symptoms of with associated basophilic stippling lead intoxication are obviously non of the red cells and elevated_retieulo- specific, their association with a his cyte counts.1, 3' 5' c' 8 The stippling and tory of pica may prove quite signifi anemia are possibly due to the inter cant. ference by lead with the incorporation COHEN AND AHRENS: CHRONIC LEAD POISONING of protoporphyrin into hemoglobin.15 A recent report of lead intoxication in adults16 notes th a t the erythroblasts in the marrow show consistent but not pathognomic changes. It has also been auggested17 th at the stipples might consist of protoporphyrin (possibly combined with lead). C oproporphyrin III is almost always found in in creased concentration in the urine of patients with chronic lead intoxica tion,3, 4' 17'20' 23 and there is a definite relationship of urinary concentration of porphyrins to the stippled red cell count but not to the degree of anemia. Lines of increased density in the metaphyses of the long bones as seen by roentgenography are almost always present in children with plum bism .3'5' 8 These lines are not diagnostic nor are they areas of increased lead deposi tion; actually they are areas of differ ential calcification.21 O ther bones may elso show " lead lines'' ; K eefer and Mokrohisky22 point out th at careful tudy of routine chest roentgenograms ny suggest the proper diagnosis. The laboratory tests which confirm * diagnosis of chronic lead poisoning Me the demonstration of abnormally high levels of lead in the blood and Ur*n e : be., above 50 to 60 jug per 100 blood, or above 80 /*g p er 1,000 ml. of urine, or per 24-hour specimen urine. In children, whose 24-hour Volume of urine excretion m ay be as *niall as 100 to 250 ml., it is more ^^^tatic to calculate lead excretion liter of urine per 24 hours. The 7 '8ree of elevation of these levels not correlate with the severity illness.1,3> * l5>19. 21. 23 ^Although there are many factors m history, physical examination, Mid no single pathognomonic finding. Chil dren may have no symptoms although their blood or urine lead concentra tions are definitely above normal. Such children might receive a diag nosis of potential, subclinical, or asymptomatic lead poisoning. The most significant data for establishing a diagnosis are a definite history of pica for lead-containing substances, suggestive signs and symptoms, anemia with stippling, " lead lines" on x-ray, increased lead and coproporphyrin levels in the urine, and increased lead concentration in the blood. The final diagnosis rests on the clinician's ju d g ment after evaluation of the data at hand. P rior to the late 1940's, treatm ent of lead intoxication was directed at shifting lead from the blood and soft tissues to the bones, whence it could be excreted more slowly and under controlled conditions. Such therapy included diets high in calcium, phos phorus, and vitamin D followed by citric and other organic acids. Since 1950, dim ercaprol (BAL) has been used with equivocal efficacy and poten tial toxicity.1,3> 4' 8' 12,19,21 In 1952, Bessman and associates24 and Belk nap31 reported on the use of calcium disodium ethylenediamine tetraacetate (versenate, edathamil, or ED TA ), a safe and effective chelating agent which binds lead into a nontoxic com plex which is easily excreted in the u rin e.3,18'20,23' 30 There has been men tion of potential toxic effects of EDTA on bone m arrow 21' 31 and renal func tion24, 30 b u t these effects may have been coincidental and certainly have not been consistently reported. Al- # ' 7j ^ -A-..---*` V 274 THE JOURNAL OF PEDIATRICS no reports of clinical bleeding dyscrasias resulting from use of this drug in therapy of plumbism. EDTA is quite effective when adm inistered intrave nously or subcutaneously, and probably when given intram uscularly, but no final agreement has been reached re garding the efficacy of its oral use. The dosage is now generally accepted to be 30 to 75 mg. per kilogram per 24 hours, but in the first published work it was 0.5 Gm. 3 times daily, regardless of weight. Most authors now suggest a plan in which the drug is given for 3 to 5 days, discontinued during a 2- or 3-dav rest period, and then given for another 3 to 5 days. Since EDTA apparently combines with lead only in body fluids and soft tis sues. the purpose of the rest period between courses of treatm ent is to al low the lead in the bone to re-establish equilibrium with the lead-depleted soft tissues. Rieders and associates20 sug gest intravenous therapy once weekly on an outpatient basis; however, cu mulative excretion studies by Chisolm and H arrison10 show th a t 4 or 5 days are required for deleading soft tis sues. D uring EDTA therapy of lead intoxication, urine lead excretion may be increased from 10 to 100 times the pretreatm ent level.18,20,23,30 H ardy and associates,20 working with adults, showed that in three normal patients the increase was only 6 to 11 fold compared with rises of 20 to 30 times in three patients with plumbism. Another good index of successful th er apy is the drop in u rin ary copropor phyrin excretion.18'20 Reduction of cerebrospinal fluid pressure by mechanical methods has generally been a last resort in treating lead encephalopathy. Techniques used with varying success have been lum bar puncture1,19 and c r a n i o t- ojny.-i.. >s. si. 22. .in R esults of more re cent work suggest that when no im provement is evident d u rin g therapy with EDTA, extensive surgical decom pression of the skull can be lifesaving and may even reduce potential resid u a l s .31 The prognosis for life in chronic lead intoxication apparently depends more on severity and duration of ill. ness than on type of th era p y .19 The usual m ortality figures range from 10 to 25 per cent2' 3' 5' *25; the fa ta l cases almost invariably were those with severe encephalopathy. The residual neurologic damage from lead intoxi cation is as distressing as the mortal ity. Significant sequelae have been re ported in from 25 to 75 p er cent of cases and include paralyses, blindness, and organic brain damage, especially in areas of visual-motor function and language skills.2' 5' 8' 10 There is a much higher incidence of severe se quelae afte r severe encephalopathy,1* but, in general, residuals are best cor related with continuing pica and, hence, continued active disease.7 DEFINITION AND CLASSIFICATION D uring the period 1950 through 1956, 43 patients were treated at Chil dren 's Hospital, W ashington, D. C., because of chronic lead poisoning. No cases of acute lead poisoning, such as is caused by inhalation of lead fumes, have been observed. In the present study the diagnosis of lead poisoning was made on the basis of abnormal blood or u rin e lead levels prior to treatm ent a n d /o r any two of the three following abnormal ities: (If pica of presumably lead-con taining m aterial, (2) punctate baso philic stippling of red blood cells on smear, or (3) markedly increased transverse densities in the metaphyses of the long bones by roentgenography. Determ inations of urine and blood lead levels were originally performed by hospital research facilities under the direction of Dr. S. 1\ Bessman, and more recently by the 1). 0 . De partment of Public Health Labora tory. No qualitative or quantitative urine coproporphvrin or stool lead studies were done. An attem pt has been made to group the patients into the following arbi trary classes: asymptomatic, lead in toxication without encephalitis, mild encephalitis, and severe encephalitis. The asymptomatic patients were chil dren who had no apparent sign or symptom of lead intoxication but, during study of families of patients with plumbism or during study for other symptoms, were discovered to have a significant accumulation of lead within their bodies. The patients with simple lead intoxication had anemia and gastrointestinal complaints such as cramps or constipation. The severe en cephalitic patients had prolonged con vulsions or coma for as long as 24 to 48 hours, while the patients with mild encephalitis had central nervous symp toms and signs not including those of severe encephalitis. T able I. T y pe s of C hronic L ead P oison ing in 43 I n fa n t s and Ch ildr en , 1950- 1956, a t C h il d r e n 's H o s p it a l , D is t r ic t of Co lu m bia Asymptomatic. Clinical syrupt out enoeph Encephalitis Mild Severe Total PA- | Itif.x t s PER C withi 8 9 12 14 17 28 32 40 19 21 Tit 100 Table I shows that approximately 28 per cent of our 43 patients were asymptomatic and 40 per cent of the children had lead encephalitis. Ob viously the proportion of encephalitis patients in any given series will color the m ortality and m orbidity of such a series and thus the effectiveness of therapy. INCIDENCE AND ETIOLOOV D istribution of cases according to age, sex, color, and season coincide, in general, with the patterns reported by other authors. The age group from 2 to 3 years contained 2* g times as many children as any other year, and the 1- to 3-year age group contained To per cent of the patients in this series. SUMMARY Of OUR YEARLY CASE DETECTION RECORD *t3 patients withchronic leadpoisoninq 1950 1951 1952 1953 1955 1955 1956 F ig\ 1.-- A n n u al incidence' of lead poison ing a t th e C h ild re n 's H o sp ita l of the D istrict of Columbia. There was no significant difference in the sex incidence in this series, but a ratio of approxim ately 3 Negroes to 1 white patient reflects the fact that our clinic and ward population is pre dom inantly Negro. F orty of the 43 patients resided in the District of Columbia. Thirty-eight of the 43 pa tients were diagnosed during the months of May through October. The recently increased yearly incidence of eases (Fig. 1) in all likelihood reflects our increased awareness and improved case finding. In 4952 and 1953, Dr. Bessman stimulated much interest at 276 THE JOURNAL OF PEDIATRICS Children's Hospital during his study of EDTA compounds and their value in therapy of chronic lead poisoning. In June, 1955, a Lead Poisoning Clinic was established, and in all probability our case finding will continue to im prove. When a history of pica is sought in children with chronic lead poison ing, it is almost always found. In this series 40 of 43 patients had a positive history of pica although in 11 of these children pica was sought only in ret rospect after other suggestive labora tory data became available. Of the 3 patients with no history of pica, the parents of 2 consistently denied any pica, while the chart of the third gave no indication th a t pica had been in quired about. Twenty-one of these 43 infants and children were studied carefully by members of our psychiatry depart ment35 who felt th a t although handto-mouth activity is a normal phase of personality development, pica, or ex cessive appetite for nonedible sub stances, should be considered abnormal after 18 months of age. In these 21 patients the average age of onset of pica was 14 months, and the average age of initial hospitalization was 31 months. Other authors have speculat ed that at least 3 months must pass from the onset of pica to the onset of symptoms of lead poisoning. In this series an average of 17 months elapsed before hospital admission. Siblings of 43 per cent, and mothers of 10 per cent, of these children also had pica. It appeared that pica in these children resembled an addiction and was usual ly selective for a particular substance. In contrast, indiscriminate pica was seen in this series only in children with severe brain damage. Paint, plaster, and new spaper were the materials most commonly ingested hv these children, but facilities for testing lead content of these materials have not been available to us. As in other series, the paint was usually on common accessible indoor m aterials such as walls, woodwork, and furnish ings. Lead nipple shields, imported cosmetics, and lead-painted cribs ivere not incriminated. The lack of appre ciation of the significance of pica was most striking in several of the families in which the children were quieted and pacified by being placed beside the favorite plaster hole. The ignorance of the dangers of pica was not con fined to parents and patients, for in one case a mother sought medical ad vice because of her child's pica and was advised to avoid conflict by per mitting him to continue. SIGNS AND SYMPTOMS The symptoms and signs of lead poisoning observed in this series of 43 patients are summarized in Table II. II.T a b l e S y m pt o m s, S ig n s, and D iagnosis on A dm ission o r 43 I n f a n t s and C hildren W it h C hronic L ead P oisoning NUMBER Sym ptom s on A dm ission Gastrointestinal Neurologic 1nfection Behavior problem Ingestion (of any foreign mater.;a l ) Other 7 09 18 17 5 4 F in din gs on A d m iss ion 1nfection Neurologic abnorm alities Normal physical examination Pallor Vomiting Allergic m anifestations Gum lines 10 17 10 6 3 o 0 L ta d P oisoning C onsidered on A dm ission Yes 28 No 15 COHEN* AND AHRENS: CHRONIC LEAD POISONING 0-;: The majority of the asymptomatic group were suspected of lead poison ing by virtue of a history of pica or a report of basophilic stippling in a peripheral blood smear while the pa tient was being treated for an infec tion. Three children were first seen after ingestion of kerosene, aspirin, and furniture polish, respectively; because of a positive history of pica, further studies were carried out. One child was admitted to the hospital by the hematology service because of a chronic anemia which had been re sistant to iron therapy for over a year; this child had a positive pica history. One child had a gait dis turbance by history; increased meta physeal densities on the roentgeno gram aroused further interest in lead poisoning. In the groups with symptomatic lead poisoning, symptoms were almost all referable to the gastrointestinal and central nervous systems. Gastroin testinal complaints included vomiting in 19, abdominal pain in 8, anorexia in 6, constipation in 3, and d iarrh ea in 2. Neurologic complaints included convulsions in 13, irritab ility in 10. other psychiatric or behavior disturb ances in 7. and gait or walking diffi culty in 4. On the basis of physical findings these children could be separated into three m ajor groups: those with infec tion as a prim ary problem (44 per cent), those with a variety of neuro logic abnormalities (39 per cent), and those with entirely normal physical findings (23 per cent). Some of the children who were seen prim arily be cause of infection also had neurologic abnormalities. The incidence of neuro logic abnormalities observed was: con vulsions in 8, coma in 5. marked ir ritability in 4, positive Babinski sign in 4, nuchal rigidity in 3, nystagm us in 2. lethargy in 2. hemiplegia in 2. optic neuritis in 2, and abducens nerve p a l s y , aphasia, spastic paraplegia, spastic extremity, central deafness, and intraocular ophthalmoplegia in 1 each. Six of the 43 children had marked pallor on admission which focused attention on the hematopoietic system. An observation that deserves particular emphasis was the absence of lead lines on the gums in all p a tients. LABORATORY DATA A summary of the pertinent labo ratory findings is presented in Table II I. Undoubtedly the two most help ful diagnostic procedures, other than lead determinations, were hematologic and roentgenographic studies. Hema tologic studies on admission were ab normal in 37 of the 43 patients. The most common abnormalities were ane mia (below 10 Gm. of hemoglobin) in 35 children, basophilic stippling in 29, and eosinophilia (above 5 per cent) in 23. Although hemolytic crises have been described, all of the patients with anemia appeared to have the typical peripheral blood smears and indices of iron deficiency. Punctate basophilia deserves comment. Not all children with lead poisoning showed stippled red cells; of those who did, one-third showed stippling only after repeated smears were examined. Obviously, it is of considerable assistance to have a properly stained and prepared blood smear, an unhurried microscopic ex amination by a trained observer, and the verbal or written statement from the clinician to the laboratory regard ing the possibility of lead poisoning. It was striking that eosinophilia was present in this series in 123 patients on at least one smear during hospital ization. Two children with eosino phil ia had allergic histories, and two had stools containing ova and para- T a b l e I I I . L a b o r a t o r y D a t a ok 41! I n f a n t s and C hildren W it h C h ro n ic L ead P oisoning Nl'MBEK I. Hematology Normal (on admission) Abnormal ( on admission) Anemia moderate (8-10 Gm. H b/100 ml.) 19 Anemia severe (below 8 Gm. H b/100 ml.) 16 Leukocvtosis (above 15,000/mm.3) 13 Basophilic stippling-- First Smear 20 later smears only 9 Eosinophilia and/or stippling 33 6 37 'rine Normal Abnormal Proteinuria Glucosuria Pvuria Hematuria 28 15 8 5 8 o Hood Sugar Normal Elevated O 5 >inal Fluid Normal Abnormal Protein increased Fells increased Sugar increased Pressure increased (Pressure normal--3) in 16 15 9 3 4 lectroencephalograni Normal ( No encephalitis Abnormal i AH encephalitis ) Focal General -ray Studv Long bone Normal Abnormal Skull Normal Abnormal Abdominal flat plate Normal Abnormal (all encephalitis) 10 7 4 37 3 34 fi 10 4 3 0 3 sites. The remainder of these patients were not carefully studied in this re spect. One might speculate on the possibility that these children with pica might also have ingested d irt which contained ova. The leukocytosis present in 13 patients was associated with infection, and did not correlate with severity of lead intoxication. Urinalyses were abnormal in slight ly over one-third of the group, but the m ajority of specimens were col lected after use of indwelling plastic catheters. Glucosuria was present in 5 children. A variety of blood chemistry tests was performed, but not in a significant number of patients. Five of 7 children tested demonstrated elevated blood sugar levels. In this regard one child had 11 urine tests positive for sugar and 3 of 10 blood sugar determ ina tions were elevated (300 mg. per 100 ml.. 165 mg. per 100 ml., and 255 mg. per 100 ml.). In this child a trial dose of insulin produced a series of convulsions and coma. Abnormal spinal fluid findings oc curred prim arily in the group with encephalitis, and spinal fluid was ob tained after onset of convulsions or coma. In some cases the spinal fluid abnormalities caused confusion as to possible aseptic meningitis or enceph alitis of viral or fungal etiology. Of the 17 patients with clinical evidence of encephalopathy, 12 had abnormal spinal fluid findings, 4 had normal spinal fluid findings, and 1 was not tested. The remaining 4 patients with abnormal spinal fluid all had clinical lead intoxication without neurologic signs or symptoms. Electroencephalograms were p e r formed in a m inority of the patients. COHEX AND AHRENS: CHRONIC LEAD POISONING 279 In 7 patients, who clinically were con sidered to have lead encephalitis, there were focal or general abnormal ities on the electroencephalogram. In none of the 10 patients designated as " asymptomatic" or " simple lead in toxication" was there any electroencephalographie abnormality. 3), and 4 skull roentgenograms dem onstrated lines of increased density. In 3 children the presenting symptoms of vomiting, abdominal pain, or ab dominal distention suggested a possible acute intestinal obstruction, but ab dominal roentgenography revealed no evidence of obstruction. However. Fig. 2.-- X-rays of the lower extremities of a patient with chronic lead poisoning, showing the increased densities at the metaphyses. Roentgenographic studies, as men tioned previously, were of considerable assistance in establishing a working diagnosis. Increased metaphyseal den sities can be seen in any of a variety of other diseases which cause a re tardation of bone growth. Neverthe less, 34 of 37 long bone roentgeno grams were interpreted as suggestive of heavy metal poisoning (Fig. 2). In this study, one chest roentgeno gram, one pelvic roentgenogram (Fig. Fig:. 3.-- X -ray of the pelvis of a patient with chronic lead poisoning: showing- increased density of Ilian casts and ischia. Also note the density of the distal end of the right twelfth rib. flecks of radiopaque m aterial seen were felt to be fragm ents of leadcontaining material (Fig. 4). For the purpose of this study, a pretreatm ent b l o o d lead level was considered suspicious in the range of 0.0(1 to 0.08 mg. per 100 ml., and toxicabove this concentration; a pretreat ment urine lead level was suspicious in the range of 0.07 to 0.15 mg. per liter per 24 hours, and toxic above THE .JOURNAL OF PEDIATRICS this range. P rio r to treatm ent, 10 of 13 children tested had suspicious or toxic blood lead levels, and 15 of 20 children tested had suspicious or toxic urine lead levels. Only 5 of these 25 abnormal specimens were obtained from patients with encephalitis; this was because the first blood or urine sample from the m ajority of encepha litic patients was collected after EDTA therapy had already been instituted. It has previously been observed that the level of lead in the blood or urine does not correlate well with the clin ical picture, and such was our expe rience in this study. It had been thought th a t the first sample of blood or urine collected after the start of EDTA therapy might show a better correlation with the clinical picture, but this was not so (Table IV ). Fig. 4.-- X - ra y of th e abdom en of a p a tie n t w ith chronic lead poisoning show ing flecks of lead-containing m aterial (p ain t) along the course of the intestines (arrow s). DIFFERENTIAL DIAGNOSES Chronic lead poisoning was con sidered as a prelim inary diagnosis in 28 of the 43 patients (65 per cent). Lead intoxication, like syphilis, sickle cell disease, and infectious mononucle osis, can affect m any systems and mimic many diseases. To illustrate this potential confusion in diagnosis, several examples might be offered. Three children were first thought to T able IV. B lood and U r in e L ead L evels B efore and A ft er EDTA T h er a py of Chronic L ead P oisoning Asymptomatic Simple intoxication Mild encephalitis Severe encephalitis Asymptomatic Simple intoxication Mild encephalitis Severe encephalitis Blood Lead Levels (mg./lOO ml.) BEFORE EDTA THERAPY 0.02-0.06 0.06-0.OS > 0.08 t ti o 3 O 1 i1 Urine Lead Levels (m g./L./24 h r.) BEFORE EDTA THERAPY <0.07 0.07-0.15 >0.15 23 32 4 3 O 1 3 3 io V DURING FIRST 24 HOURS OF EDTA THERAPY 0.8 1.2 1.2-1.6 > 1.6 i i 1i 12 DURING FIRST 24 HOURS OF EDTA THERAPY 0.7-1.5 1.5-2.2 2.2-3.0 >3.0 1 3 11 1 11 21 1 2 COHEN AND AHRENS: CHRONIC LEAD POISONING have acute abdominal disease with possible intestinal obstruction; one child had a resistant anemia; one was treated as a diabetic. Poliomyelitis was diagnosed in another child with a spastic paraplegia resulting from chronic intoxication. It is of interest that children differ from" ffdtilts with chronic plumbism in that the ch ild 's lower extremities are more commonly affected than his upper extremities. MORTALITY AND PATHOLOGY Three children (7 per cent) died (all with severe encephalopathy) after an average of 2% days of hos pitalization. Gross pathological diag noses on one of these children13 were edema and congestion of the brain, hepatic failure, pulmonary hemor rhage, and aseariasis. There were gross an d /o r microscopic changes in the liver, kidneys, and brain. Chemical analysis in this single case revealed the following lead concentrations (in mil ligrams per 100 grams of tissue) : bone 9.96, kidney 0.8, liver 0.78, lung 0.10, brain 0.00. This reflects the p re viously noted poor correlation be tween clinical lead encephalopathy and chemical analysis of brain tissue. In the presence of marked anemia, the bone marrow of 2 children demon strated marked ervthroid hyperplasia. THERAPY This group of patients with chroniclead poisoning was treated with EDTA. X o BAL was used. EDTA was given either intravenously or subcutaneously in the standard dosage of 30 ing. per kilogram per day; in the first 18 eases 0.5 Gin. was given 3 times daily regardless of weight. EDTA was given for 5 days, discon tinued for 3 days, and then repeated for 5 days. In the present series no ev idence of local or systemic toxicity from EDTA has been noted. In gen eral, treatm ent has been dictated by the clinical status of the individual since the results of the chemical studies for lead were usually not reported for 1 to 2 weeks and then frequently did not correlate well with the sever ity of the symptoms. The most criti cal problem in therapy is the manage ment of the child with lead encepha lopathy who is in status epilepticus or coma. Craniotomy and reduction of spinal fluid pressure by repeated lum bar puncture have not been used con sistently in our patients and we have too few data on which to base con clusions as to their efficacy. Inten sive supportive nursing care, paren teral anticonvulsants, restricted paren teral fluids, and parenteral EDTA have been the mainstays of therapy. Oral ED TA has not been used in recent years because prelim inary work showed very little promise. CASE FOLLOW-UP Follow-up of this group of patients is shown in Table V. It is im portant to note that one-fourth of the patients have been lost to follow-up. The per sistence of pica, which would seem the crux of the problem, has unfortu nately not been adequately followed, although our lead clinic is vigorously pursuing this problem now. In light of the thought that the severe neuro logic residuals of lead encephalopathy might be due to repeated or continued poisoning, our series may be signifi cant in that only 1 of 43 children went to a convalescent or lead-free home on discharge from the hospital. The other children returned to their parents and previous environments. It would os -> THE .JOURNAL OF PEDIATRICS seem that safer housing for the entire family would be more feasible than the use of convalescent homes in prevent ing recurrent plumbism. This, of course, brings the problem into the realm of public health, sociology, and the law. We have seen recently that our social worker has been able to give, affected families effective help in finding more satisfactorv housing. techniques.35 As a result of those eval uations, the children were classified as having severe, moderate or no or ganic psychiatric residuals. It was the consensus of these workers that psychologic testing was the most effi cient method of assessing mild to moderate degrees of organic brain damage. Three children were not tested psychologically, and on the basis T a b le V. F o l l o w -u p ok 43 P a t ie n t s W it h C h r o n ic L ead P o is o n !no Death ICo follow-up Follow-up Pica continued Pica stopped Pica unknown Well Moderate res: dual Severe residual CLINICAL . SYMPTOMS NO ASYMPTOMATIC ENCEPHALITIS i 00 45 89 oo 14 53 5s 31 00 ENCEPHALITIS MILD SEVERE 03 9n (i 6 93 91 99 30 01 35 T<>TAL 3 11 29 9 .8 12 lfi 5 8 In this series of 43 patients, 3 chil dren died and at least 13 others have moderate or severe neurologic and or psychologic residuals. Of the group of 17 children with encephalitis, 2 have not been followed, 3 ai'e well, 9 have moderate or severe residuals, and 3 are dead. Forty-five per cent of the 29 children who survived and were followed up show residuals. This is a far grimmer picture than that painted by other recent reports2- 3- s- 10- 1!l and merits further study. The use of psy chologic studies in this series may. perhaps, account for a part of the dif ference. A group of 21 children who had re covered from lead intoxication were evaluated here on the basis of inter views with the parents, playroom ses sions with the child, and by psycho logic testing in the realms of intelli gence. social m aturity, and projective of other studies it could not be deter mined whether they had no residuals or moderate residuals. Of the remain ing 13 children, 8 had had encepha litis. and all had residuals (1 moderate and 7 severe). Of the 10 children who had had lead poisoning without en cephalitis. 5 had moderate residuals and f> had none. It is impossible, of course, to be certain how much of this brain damage is a result of the lead poisoning and how much may have preceded it. Wc know that one child was definitely retarded before the on set of his lead poisoning; 3 others had histories compatible with possible pre-existing damage, e.g.. traum atic premature birth or bizarre autistictype behavior. All 4 of these children fell into the group with severe residu als. Nevertheless, the residual morbid ity resulting directly from chronic lead poisoning is tru ly shocking. The COHEX AND AHRENS: CHRONIC LEAD POISONING variation between our results and those in the literature may suggest any of the following: ( 1 ) a difference in the population studied. (2 ) signifi cant difference in therapy, (2 ) differ ence in the m easuring devices and norms in the follow-up of these chil dren. or (4) a combination of all these factors. We feel that the th ird alter native is the most plausible in the problem of plumbism. The Lead Poisoning Clinic, which was established as a result of interest at this hospital in the problem of plumbism. is staffed by a team con sisting of a pediatrician, a pediatric resident, a psychiatrist, a psychologist, and a social worker. The clinic pro vides a means of screening all pica cases, of standardizing in-patient th e r apy, and of better following patients discharged after treatm ent. When necessary, psychiatric assistance has been offered w ith greater parental ac ceptance of the team approach than of direct psychiatric referral alone. With psychiatric help, many of the parents are better able to handle their chil dren's needs, and as the pica of these children becomes less of a problem, their lead intoxication tends to disap pear. SUMMARY AND CONCLUSIONS The experience at Children's Hos pital in the management of 44 children with chronic lead poisoning over a 7-vear period is presented. The ob served m ortality of 7 per cent in 43 patients is significantly high even though it is an improvement over that noted in many previous reports. More im portant, the 45 per cent incidence of neurologic and psychiatric residual morbidity deserves serious considera tion and further studv. Chronic lead poisoning has become an increasingly significant problem as awareness of the diagnosis, treatment, and residuals has increased. Because lead enceph alitis is an im portant killer and crip- plcr of children, early diagnosis and therapy (with KDTA). as well as adequate and continued follow-up. are essential. The simple expedient of routine inquiry into the presence of pica will bring to light many cases of plumbism before they become symp tomatic. Furtherm ore, counseling di rected at cessation of pica seems to be an effective tool in prevention of con tinued lead poisoning. 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